Effectiveness of Standard-Dose Thromboprophylaxis with Enoxaparin in Preventing Recurrent Venous Thromboembolism in Pregnancy

Introduction. Pregnancy-associated venous thromboembolism (PA-VTE) is recognised as a leading cause of maternal mortality worldwide. There is no international consensus on the optimal thromboprophylaxis strategy in pregnancy. A previous study reported recurrent VTE rates of up to 5.5% in high-risk women despite daily thromboprophylaxis. (Roeters van Lennep et al, J Thromb Haemost 2011; 9:473-80). This study prompted development of a randomised control trial that compares rates of thrombosis using standard-dose LMWH thromboprophylaxis to weight-adjusted intermediate dose LMWH in women at risk of PA-VTE.

Method. A retrospective cohort study of women who received thromboprophylaxis for prevention of PA-VTE at National Women's Health, Auckland City Hospital between 1998 and 2014. Women were identified using the records of special authority requests for enoxaparin and hospital pharmacy dispensing records. Ethics approval was obtained. Data was collected on patient demographics, VTE risk factors, dose and duration of enoxaparin therapy, PA-VTE rates, haemorrhagic complications, and obstetric and neonatal outcomes. Exclusions included women given therapeutic or intermediate-dose enoxaparin, those on lifelong anticoagulation, those who received enoxaparin solely for obstetric indications, or those who received it for a limited duration for a transient risk factor. Women received thromboprophylaxis either for six-weeks postpartum only or both antenatally and for six-weeks postpartum, according to local clinical practice.

Results Of 157 women who received enoxaparin during pregnancy or in the postpartum, we identified a cohort of 124 women who had 173 pregnancies after exclusions (Figure 1). Of these, 65.5% (n=82) of women had personal history of VTE, the majority (n=57; 69.5%) provoked by either pregnancy or hormonal therapy, 20.7% (n=17) by other factors and 6.4% (n=8) were unprovoked. Eighteen (22.0%) women with previous VTE had an inherited thrombophilia. Of 43 women with no personal history of VTE, 28 (34.4%) women had a family history of VTE, 25 (89.3%) with an inherited thrombophilia. Of 87 pregnancies to women with a history of unprovoked VTE or VTE provoked by pregnancy or hormonal therapy, both antenatal and postpartum thromboprophylaxis was given (79.3%). Standard doses of enoxaparin (40mg) were given in 95.4% of pregnancies, a smaller number given higher (1.2%) and lower (3.5%) doses. One deep vein thrombosis (0.6%) was recorded in a woman of normal weight taking 40mg enoxaparin.

Discussion. Higher rates of recurrent VTE (5.5%) are reported in a retrospective cohort of 126 pregnancies in 91 women considered to be at risk of PA-VTE who received thromboprophylaxis predominantly with nadroparin 2850U. An important difference in approach to thromboprophylaxis between our groups was that women with previous VTE in association with pregnancy and hormonal contraception did not routinely receive antenatal thromboprophylaxis but only postpartum. Women in 18 pregnancies in our cohort would not appear to have been recommended thromboprophylaxis in pregnancy following their approach.

Conclusions. In this retrospective cohort study of pregnant women at risk of recurrent VTE, we found much lower breakthrough rate of VTE than has previously been reported, at only 0.6%. The majority of women (95.4%) received standard low dose enoxaparin which was not adjusted for perceived VTE risk or weight. These findings call into question the rationale for administering intermediate-dose LMWH to women at high risk of PA-VTE.